Method of improving microcirculation and treating senility with beta-(pyridyl lower alkyl)-amines



United States Patent 3,439,096 METHOD OF IMPROVING MICROCIRCULATION AND TREATING SENILITY WITH BETA-(PYRI- DYL LOWER ALKYL)-AMINES Spencer M. Fossel, Morristown, N.J., assignor to Uninied, Inc., Morristown, NJ. No Drawing. Filed Sept. 9, 1965, Ser. No. 486,237 Int. Cl. A61k 27/00 U.S. Cl. 424-263 8 Claims ABSTRACT OF THE DISCLOSURE This invention relates to the improving of microcirculation and to the treatment of senility, and more partiularly to oral treatments to treat microcirculation and senility, according to which invention a beta-(2-pyridyllower alyl)-amine is administered in order to achieve these results.

The microcirculatory or microvascular system is generally described as consisting of all vessels with an internal diameter of 100 microns or less. It is possible by microscopy, but not by the naked eye, to see the characteristics of capillary circulation or microcirculation. The tiny vessels through which microcirculation takes place are really only endothelial tubes with no powers of contraction.

In recent times more and more emphasis has been placed on microcirculation as a factor in various diseases, among which is included senility.

Apparently, alterations or failure of flow within the microv-ascular system account for the failure of tissue or organ function in a variety of common clinical conditions. The microcirculation may be comprised by either arterial occlusions or venous occlusions. In both cases the capillary network immediately ahead or behind the plug will be blocked. Vast numbers of capillary vessels may be obstructed to involve almost an entire organ, and yet central or large vessel flow may give no indication of this.

Since the specific and non-specific functions of all cells depend on proper nutrition and elimination of undesirable metabolites, impairment of the blood supply as a result of impaired microcirculation could affect cells directly.

Most regulatory substances used to try to establish normal balance between the vasodilator and vasoconstrictor agents are very powerful drugs which cause imbalances which have an undesired marked effect on the microcirculation system.

It is generally considered that impaired microcirculation is to a great extent mediated by histamine. Induced histamine is believed to be newly synthesized in free, pharmacologically active form, in or near the vascular endothelial cells. As a consequence, attempts have been made to use histamine to overcome impaired microcirculation.

However, histamine can only be administered by injection, and in addition, the dosages of histamine must be very carefully regulated because overdosages of histamine are highly toxic and may be fatal.

It is accordingly a primary object of the present invention to provide for an oral composition and method of oral administration to improve impaired microcirculation.

It is yet another object of the present invention to provide a method of treating senility.

It is still a further object of the present invention to provide a method of improving impaired microcirculation by oral administration with a minimum of toxic dangers due to overdosages.

Other objects and advantages of the present invention will be apparent from a further reading of the specification and of the appended claims.

3,439,096 Patented Apr. 15, 1969 With the above and other objects in view, the present invention mainly comprises a method of improving impaired microcirculation by administration of a compound selected from the group consisting of )8-(2-pyridyl lower alkyl)-amines, B-(4-pyridyl lower alkyl)-amines and nontoxic acid addition salts thereof.

The administration of the 8-(2- or 4-pyridyl lower alkyl)-amines, or their non-toxic acid addition salts is preferably effected orally using a rnicrocirculation-improving effective amount thereof.

The lower alkyl portion of the pyridyl alkyl amines of the invention may be any alkyl of up to 5 carbon atoms. The most preferred alkyl groups are methyl and ethyl. Among the most preferred compounds are B-(2-pyridyl)- ethyl methyl amine, fl-(4-pyridyl)-ethyl methyl amine, l-(2-pyridyl)2methyl amino propane, and non-toxic acid addition salts thereof such as the hydrochloride, the tartrate, the fumarate, the gluconate, etc.

It has been found that the ,8-(2- or 4-pyridyl alkylamines in low dosages, which may be administered orally, are highly effective in improving impaired microcirculation and in the treatment of senility.

The 3-(2- or 4-pyridyl alkyl)-amines of the present invention may be administered in amounts as low as 0.5 mg. per day and as high as 4550 mg. per day to achieve the effects of the present invention. The compounds are preferably administered in an amount of about 4-45 mg, per day, more preferably in an amount of 12-45 mg. per day, and most preferably in a unit dose of about 4-15 mg. administered three times a day. The same can be administered either orally or by injection, the preferred administration route being by oral administration.

The 5-(2- or 4-pyridyl alkyl)-amines of the invention are preferably administered in the form of a non-toxic acid addition salt thereof, and most preferably in the form of the hydrochloride.

The following examples are given to further illustrate the present invention. The scope of the invention is not, however, meant to be limited to the specific details of the examples.

Example 1 Tablets are prepared by usual tabletting procedure, each tablet containing:

fi-(Z-pyridyD-ethyl methyl amine hydrochloride, 5 mg. Calcium carbonate q.s., 1 g.

The above tablet can be administered in all conditions requiring improved microcirculation. Administration of the above tablet has been found to be effective in the treatment of senility.

In connection with the treatment of senility, senile patients were subjected to treatment using the above tablets, administered three times a day, over a period of twelve weeks. At the end of six weeks of administration an observable change becomes manifest.

If the therapy is discontinued by administration of a placebo, the patients return to pretreatment status.

In connection with tests carried out, a psychologist evaluating the tests on various patients was convinced that the material was of no value because three of the original patients during the last six weeks of treatment had slipped back to their pretreatment status. The psychologist, however, did not known that the patients had been on placebos during the last six weeks of the tests.

Example 2 Tablets are prepared by usual tabletting procedure, each tablet containing:

fl-(2-pyridyl)-ethyl methyl amine hydrochloride, 10 mg. Lactose q.s., l g.

The above tablet is highly effective in improving impaired microcirculation and in thetreatment of senility.

Example 3 Ampoules are prepared each containing 10 cc. and each cc. consisting of mg. 1-(2-pyridyl)-2-methyl amino propane hydrochloride dissolved in 0.9% sodium chloride solution. This solution can be administered parenterally to improve impaired microcirculation, and also in the treatment of senility It is believed that from the foregoing, adaptations and variations of the invention can be made without departing from the spirit or scope of the invention. Such adaptations and variations are of course intended to be comprehended within the meaning and scope of equivalents of the present invention.

What is claimed as new and desired to be secured by Letters Patent is:

1. Method of improving impaired microcirculation, which comprises administering to a subject requiring the same a microcirculation-improving effective amount of at least one member selected from the group consisting of BQ-pyridyl-lower alkyl)-amine, fi-(4-pyridyl-1ower alkyl)-amine and non-toxic acid addition salts thereof.

2. Method of improving impaired microcirculation, which comprises orally administering to a subject requiring the same a microcirculation-improving effective amount of at least one member selected from the group consisting of B (2 pyridyl lower alkyl) amine, 5-(4- pyridyl-lower alkyl)-amine and non-toxic acid addition salts thereof.

3. Method of improving impaired micro-circulation, which comprises administering to a subject requiring the same at least one member selected from the group consisting of ,B-(Z-pyridyl-lower alkyl)-amine, [3-(4-pyridyllower alkyl)-amine and non-toxic acid addition salts thereof in an amount of about 0.5-45 mg. per day.

4. Method of improving impaired micro-circulation, which comprises orally administering to a subject requiring the same at least one member selected from the group consisting of B-(Z-pyridyl-lower alkyl)-amine, p-(4-pyridyl-lower alkyl)-amine and non-toxic acid addition salts thereof in an amount of about 0.5- mg. per day.

5. Method of treating senility, which comprises administering to a senile patient an effective amount of at least one member selected from the group consisting of fl-(2-pyridyl-1ower alkyl)-amine, B-(4-pyridyl-lower alkyl)- amine and non-toxic acid addition salts thereof.

6. Method of treating senility, which comprises administering to a senile patient by oral administration an effective amount of at least one number selected from the group consisting of ,B-(Z-pyridyl-lower alkyl)-amine, B-(4-pyridyl-lower alkyl)-amine and non-toxic acid addition salts thereof.

7. Method of treating senility, which comprises administering to a patient at least one member selected from the group consisting of B-(Z-pyridyl-lower aIkyD-amine, p-(4-pyridyl-lower alkyl)-amine and non-toxic acid addition salts thereof in an amount of about 05-45 mg. per day.

8. Method of treating senility, which comprises orally administering to a patient at least one member selected from the group consisting of ,B-(Z-pyridyl-lower alkyl)- amine, fl-(4pyridyl-lower alkyl)-amine and non-toxic acid addition salts thereof in an amount of about 0.5-45 mg. per day.

References Cited UNITED STATES PATENTS 4/1966 Mull. 5/1966 Mull.

Disclaimer 3,439,096.Spencer M. Fossel, Morristown, NJ. METHOD OF IMPROV- ING MICROCIRCULATION AND TREATING SENILITY WITH BETA(PYRIDYL LOWER ALKYL) AMINES. Patent dated Apr. 15, 1969. Disclaimer filed Dec. 2, 1968, by the assignee, Um'med, Inc.

Hereby disclaims the terminal portion of the term of the patent subsequent to Sept. 15, 1981.

[Ofiicz'al Gazette June 17, 1.969.] 

